Tmem138, encoding a putative transmembrane protein, is linked to ciliopathies. It localizes to the ciliary transition zone, playing a crucial role in molecular trafficking, especially between the inner and outer segments in photoreceptors. This function is vital for photoreceptor function and overall eye health [1,2,3,4].

Genetically inactivating mouse Tmem138 in germline deletion led to abolished outer segment (OS) morphogenesis and rapid photoreceptor degeneration. Tmem138 was required for Ahi1 localization to the distal subdomain of the connecting cilium (CC) in photoreceptors. Rhodopsin, an OS protein, was mislocalized throughout the mutant cell body before OS morphogenesis. Ablation of Tmem138 in mature rods also caused failure of disc renewal and OS disintegration. Additionally, Tmem138 interacts with rhodopsin and Tmem231, and the ciliary localization of Tmem231 was altered in mutant photoreceptors [1].

In conclusion, Tmem138 is essential for the functional organization of the CC, which is crucial for rhodopsin localization and OS biogenesis. Mouse models with Tmem138 knockout have revealed its significance in preventing retinal dystrophies associated with CC defects, providing insights into ciliopathy-related retinal degenerations [1].

References:

1. Guo, Dianlei, Ru, Jiali, Xie, Lijing, Liu, Yizhi, Liu, Chunqiao. 2022. Tmem138 is localized to the connecting cilium essential for rhodopsin localization and outer segment biogenesis. In Proceedings of the National Academy of Sciences of the United States of America, 119, e2109934119. doi:10.1073/pnas.2109934119. https://pubmed.ncbi.nlm.nih.gov/35394880/

2. Bruel, Ange-Line, Franco, Brunella, Duffourd, Yannis, Faivre, Laurence, Thauvin-Robinet, Christel. 2017. Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes. In Journal of medical genetics, 54, 371-380. doi:10.1136/jmedgenet-2016-104436. https://pubmed.ncbi.nlm.nih.gov/28289185/

3. Li, Chunmei, Jensen, Victor L, Park, Kwangjin, Valente, Enza Maria, Leroux, Michel R. 2016. MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone. In PLoS biology, 14, e1002416. doi:10.1371/journal.pbio.1002416. https://pubmed.ncbi.nlm.nih.gov/26982032/

4. Lee, Jeong Ho, Silhavy, Jennifer L, Lee, Ji Eun, Zaki, Maha S, Gleeson, Joseph G. 2012. Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. In Science (New York, N.Y.), 335, 966-9. doi:10.1126/science.1213506. https://pubmed.ncbi.nlm.nih.gov/22282472/